| Structural highlights
Function
MUS81_HUMAN Interacts with EME1 and EME2 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, replication forks and nicked Holliday junctions. May be required in mitosis for the processing of stalled or collapsed replication forks.[1] [2] [3] [4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
The MUS81-EME1 endonuclease maintains metazoan genomic integrity by cleaving branched DNA structures that arise during the resolution of recombination intermediates. In humans, MUS81 also forms a poorly characterized complex with EME2. Here, we identify and determine the structure of a winged helix (WH) domain from human MUS81, which binds DNA. WH domain mutations greatly reduce binding of the isolated domain to DNA and impact on incision activity of MUS81-EME1/EME2 complexes. Deletion of the WH domain reduces the endonuclease activity of both MUS81-EME1 and MUS81-EME2 complexes, and incisions made by MUS81-EME2 are made closer to the junction on substrates containing a downstream duplex, such as fork structures and nicked Holliday junctions. WH domain mutation or deletion in Schizosaccharomyces pombe phenocopies the DNA-damage sensitivity of strains deleted for mus81. Our results indicate an important role for the WH domain in both yeast and human MUS81 complexes.
A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes.,Fadden AJ, Schalbetter S, Bowles M, Harris R, Lally J, Carr AM, McDonald NQ Nucleic Acids Res. 2013 Aug 27. PMID:23982516[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chen XB, Melchionna R, Denis CM, Gaillard PH, Blasina A, Van de Weyer I, Boddy MN, Russell P, Vialard J, McGowan CH. Human Mus81-associated endonuclease cleaves Holliday junctions in vitro. Mol Cell. 2001 Nov;8(5):1117-27. PMID:11741546
- ↑ Constantinou A, Chen XB, McGowan CH, West SC. Holliday junction resolution in human cells: two junction endonucleases with distinct substrate specificities. EMBO J. 2002 Oct 15;21(20):5577-85. PMID:12374758
- ↑ Ogrunc M, Sancar A. Identification and characterization of human MUS81-MMS4 structure-specific endonuclease. J Biol Chem. 2003 Jun 13;278(24):21715-20. Epub 2003 Apr 9. PMID:12686547 doi:https://dx.doi.org/10.1074/jbc.M302484200
- ↑ Ciccia A, Constantinou A, West SC. Identification and characterization of the human mus81-eme1 endonuclease. J Biol Chem. 2003 Jul 4;278(27):25172-8. Epub 2003 Apr 29. PMID:12721304 doi:https://dx.doi.org/10.1074/jbc.M302882200
- ↑ Blais V, Gao H, Elwell CA, Boddy MN, Gaillard PH, Russell P, McGowan CH. RNA interference inhibition of Mus81 reduces mitotic recombination in human cells. Mol Biol Cell. 2004 Feb;15(2):552-62. Epub 2003 Nov 14. PMID:14617801 doi:https://dx.doi.org/10.1091/mbc.E03-08-0580
- ↑ Zhang R, Sengupta S, Yang Q, Linke SP, Yanaihara N, Bradsher J, Blais V, McGowan CH, Harris CC. BLM helicase facilitates Mus81 endonuclease activity in human cells. Cancer Res. 2005 Apr 1;65(7):2526-31. PMID:15805243 doi:https://dx.doi.org/10.1158/0008-5472.CAN-04-2421
- ↑ Ciccia A, Ling C, Coulthard R, Yan Z, Xue Y, Meetei AR, Laghmani el H, Joenje H, McDonald N, de Winter JP, Wang W, West SC. Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM. Mol Cell. 2007 Feb 9;25(3):331-43. PMID:17289582 doi:https://dx.doi.org/S1097-2765(07)00007-X
- ↑ Munoz IM, Hain K, Declais AC, Gardiner M, Toh GW, Sanchez-Pulido L, Heuckmann JM, Toth R, Macartney T, Eppink B, Kanaar R, Ponting CP, Lilley DM, Rouse J. Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair. Mol Cell. 2009 Jul 10;35(1):116-27. PMID:19595721 doi:S1097-2765(09)00433-X
- ↑ Svendsen JM, Smogorzewska A, Sowa ME, O'Connell BC, Gygi SP, Elledge SJ, Harper JW. Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell. 2009 Jul 10;138(1):63-77. PMID:19596235 doi:S0092-8674(09)00777-6
- ↑ Fadden AJ, Schalbetter S, Bowles M, Harris R, Lally J, Carr AM, McDonald NQ. A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes. Nucleic Acids Res. 2013 Aug 27. PMID:23982516 doi:10.1093/nar/gkt760
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